College of Basic Medicine and Biological Sciences, Medical Department, Soochow University, 215123, Suzhou, People's Republic of China.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
J Nanobiotechnology. 2021 Nov 18;19(1):376. doi: 10.1186/s12951-021-01129-3.
BACKGROUND: Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine.
gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model.
gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy.
We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments.
背景：胞嘧啶-磷酸-鸟嘌呤（CpG）二核苷酸已被用作癌症免疫疗法的佐剂。然而，未经修饰的 CpG 在临床试验中效率不高。葡萄糖是 C 型凝集素受体（CLRs）的配体，可以促进 DC 成熟和抗原呈递，这是诱导适应性免疫反应的第一步。因此，将 B 型 CpG DNA 与含葡萄糖的糖聚合物偶联可能会通过基于 CpG 的疫苗增强对肿瘤的治疗效果。
gCpG 通过 B 型 CpG DNA 与含葡萄糖的糖聚合物的化学偶联而开发。在原发性黑色素瘤模型及其转移模型中测试了 gCpG 疫苗的治疗效果。
基于 gCpG 的肿瘤疫苗抑制了小鼠的原发性和转移性黑色素瘤，这依赖于 CD8+T 细胞和 IFNγ。在肿瘤微环境中，gCpG 处理增加了 Th1 和 CTL 的浸润，增加了 M1 巨噬细胞，减少了 Tregs 和 MDSCs 群体，并促进了具有增强的 IFNγ和 TNFα分泌的炎症环境。当与抗 PD1 免疫疗法联合使用时，gCpG 的抗肿瘤功效大大增强。
我们证实 gCpG 通过激活肿瘤特异性 Th1 和 Tc1 反应以及调节肿瘤微环境，是一种有前途的疫苗佐剂。
